| First Author | Jiang L | Year | 2013 |
| Journal | Kidney Int | Volume | 84 |
| Issue | 2 | Pages | 285-96 |
| PubMed ID | 23515048 | Mgi Jnum | J:324499 |
| Mgi Id | MGI:6832448 | Doi | 10.1038/ki.2013.80 |
| Citation | Jiang L, et al. (2013) A microRNA-30e/mitochondrial uncoupling protein 2 axis mediates TGF-beta1-induced tubular epithelial cell extracellular matrix production and kidney fibrosis. Kidney Int 84(2):285-96 |
| abstractText | Mitochondria dysfunction has been reported in various kidney diseases but how it leads to kidney fibrosis and how this is regulated is unknown. Here we found that mitochondrial uncoupling protein 2 (UCP2) was induced in kidney tubular epithelial cells after unilateral ureteral obstruction in mice and that mice with ablated UCP2 resisted obstruction-induced kidney fibrosis. We tested this association further in cultured NRK-52E cells and found that TGF-beta1 remarkably induced UCP2 expression. Knockdown of UCP2 largely abolished the effect of TGF-beta1, whereas overexpression of UCP2 promoted tubular cell phenotype changes. Analysis using a UCP2 mRNA-3'-untranslated region luciferase construct showed that UCP2 mRNA is a direct target of miR-30e. MiR-30e was downregulated in tubular cells from fibrotic kidneys and TGF-beta1-treated NRK-52E cells. A miR-30e mimic significantly inhibited TGF-beta1-induced tubular-cell epithelial-mesenchymal transition, whereas a miR-30e inhibitor imitated TGF-beta1 effects. Finally, genipin, an aglycone UCP2 inhibitor, significantly ameliorated kidney fibrosis in mice. Thus, the miR-30e/UCP2 axis has an important role in mediating TGF-beta1-induced epithelial-mesenchymal transition and kidney fibrosis. Targeting this pathway may shed new light for the future of fibrotic kidney disease therapy. |
